Amphiregulin/epiregulin mRNA Expression and Primary Tumor Location in Colorectal Cancer

Anticancer Res. 2019 Sep;39(9):4729-4736. doi: 10.21873/anticanres.13655.

Abstract

Background/aim: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine the relationship between AREG, EREG mRNA expression levels and tumor location as well as the efficacy of anti-EGFR antibody agents.

Materials and methods: Real-time PCR was used to assess AREG and EREG mRNA expression in metastatic colorectal cancer (CRC) samples from 153 patients.

Results: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who received anti-EGFR antibody, response rates were significantly higher in AREGHigh than in AREGLow In the left-sided tumor group, overall survival was significantly longer in patients with high EREG levels than with low levels, whereas the right-sided tumor group showed no survival difference between them.

Conclusion: AREG and EREG mRNA expression levels in left-sided CRC were higher than in right-sided tumors. This may help explain why left-sided CRC is more responsive to anti-EGFR antibodies.

Keywords: Amphiregulin (AREG); anti-EGFR antibody; colorectal cancer; epiregulin (EREG); tumor location.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amphiregulin / genetics*
  • Antineoplastic Agents, Immunological / pharmacology
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Epiregulin / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Organ Specificity / genetics
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA, Messenger / genetics*

Substances

  • AREG protein, human
  • Amphiregulin
  • Antineoplastic Agents, Immunological
  • Epiregulin
  • RNA, Messenger
  • Proto-Oncogene Proteins p21(ras)